51 results about "Valproic Acid" patented technology

The invention belongs to the technical field of separation of drug intermediates, and particularly relates to a control method for a process impurity 2-ethyl valeric acid (EP-B) in preparation of valproic acid or sodium valproate by a diethyl malonate method. According to the method disclosed by the invention, the content of 2-ethyl-2-propylmalonic acid process impurities in dipropylmalonic acid is controlled, so that the content of 2-ethylvaleric acid (EP-B) which is a process impurity in valproic acid or sodium valproate is accurately controlled; adding a polar solvent into the dipropylmalonic acid crude product, heating, pulping for a certain time, cooling, filtering and drying to obtain a high-purity dipropylmalonic acid refined product; high-purity valproic acid (RRT is equal to 1.00) is prepared through decarboxylation of the dipropyl malonic acid fine product, and the purity is 99.779%; 0.020% of 2-ethyl valeric acid (RRT is equal to 0.90); and valeric acid (RRT = 0.77), 0.039%. The valproic acid product quality meets the requirements of European Pharmacopoeia. According to the method, the problems of quality control and process evaluation of valproic acid or sodium valproate prepared by a diethyl malonate method are solved.

The invention belongs to the technical field of separation of drug intermediates, and particularly relates to a method for preparing a high-purity dipropylmalonic acid refined product by adding a polar solvent into a dipropylmalonic acid crude product, heating, pulping for a certain time, cooling, filtering and drying. Decarboxylating the refined dipropylmalonic acid product to obtain high-purity valproic acid; distilling the filtrate to recover the polar solvent to obtain 2-methyl-2-propylmalonic acid, and carrying out decarboxylation on the 2-methyl-2-propylmalonic acid to obtain 2-methylpentanoic acid; 2-methylvaleric acid is used as a perfume additive. According to the method disclosed by the invention, the process impurity 2-methyl-2-propylmalonic acid in dipropylmalonic acid is separated, and the process impurity 2-methylvaleric acid (EP-L) in valproic acid or sodium valproate is precisely separated; the quality of the valproic acid product prepared by the method disclosed by the invention meets the requirements of European Pharmacopoeia EP-11 (2023). According to the invention, the problems of quality control and process evaluation of valproic acid or sodium valproate prepared by a dimethyl malonate method are solved.

The invention discloses application of Trolox in preparation of a medicine for treating toxicity caused by valproic acid, and belongs to the technical field of biological medicine. The invention discovers for the first time that Trolox has a new medicine application of preventing and / or treating developmental toxicity caused by valproic acid or redox level imbalance caused by valproic acid; furthermore, animal experiments prove that Trolox can relieve zebra fish development malformation caused by valproic acid and also can relieve zebra fish redox level imbalance caused by valproic acid; this provides a new solution for the prevention and / or treatment of developmental toxicity caused by valproic acid or redox level imbalance caused by valproic acid.

The invention provides application of injectable bioactive hydrogel in treatment of recurrent abortion, and relates to the technical field of biomedicine, and the technical key points are as follows: aldehydic hyaluronic acid and chitosan are connected in parallel, the injectable bioactive hydrogel is developed, and the hydrogel is loaded with LIF, VEGF, IL-11 and valproic acid to enhance regeneration activity. According to the application, the effect is evaluated in vitro through a specific verification experiment. Results show that the hydrogel prepared by the application shows rapid gelation, good biocompatibility and factor loading capacity, and enhances the proliferation of human endometrial stromal cells and the vascularization capacity of human umbilical vein endothelial cells. In macrophages, the expression of a proinflammatory cytokine is down-regulated, and the expression of an anti-inflammatory cytokine IL-10 is up-regulated. In conclusion, the HA-CHO / chitosan hydrogel in the application supports endometrial regeneration by synergistically promoting proliferation, angiogenesis, immune regulation and receptivity.

The present invention relates to a pharmaceutical composition for oral administration, the pharmaceutical composition comprising: a) immediate-release granules comprising i. an active ingredient selected from the group consisting of valproic acid, semi-sodium valproic acid, sodium valproic acid, and magnesium valproic acid, and ii. a filler; and b) sustained-release pellets comprising: i. a pellet core comprising (1) an active ingredient selected from the group consisting of valproic acid, semi-sodium valproic acid, sodium valproic acid, and magnesium valproic acid, and (2) a filler; and ii. on the pellet core iii. A sustained-release pellet comprising a subcoat provided on the subcoat, the content of which is 10 to 20% by weight based on the weight of the pellet core and contains a film-forming agent, and iii. a sustained-release coating provided on the subcoat, the content of which is 25 to 100% by weight based on the weight of the pellet core coated with the subcoat and contains a film-forming agent, wherein the amount of active ingredient in the immediate-release granules accounts for 70 to 80% by weight of the total weight of active ingredients in the pharmaceutical composition, and the amount of active ingredient in the sustained-release pellets accounts for 20 to 30% by weight of the total weight of active ingredients in the pharmaceutical composition. In yet another aspect, the present invention relates to a method for producing a pharmaceutical composition and a pharmaceutical composition for use in a method of pretreatment of cancer.

The present invention relates to methods of treating / preventing abnormal conditions associated with pulmonary arterial hypertension (PAH) and methods of treating PAH in subjects refractory to treatment for PAH, said methods involving administering to the subject of an effective amount of a of Formula (I), wherein R1 is either H or D and wherein D is deuterium, or a pharmaceutically acceptable salt thereof.

The invention belongs to the field of pharmaceutical chemical engineering and fine chemical engineering, and relates to a method for recovering 2-cyano-2-methylvaleric acid as shown in a chemical structural formula I. The method comprises the following steps: selecting methyl 2-cyanoacetate and 1-chloropropane, and carrying out catalytic dipropylation under the action of potassium carbonate to prepare methyl 2-cyano-2-valproate; hydrolyzing the latter to obtain 2-cyano-2-valproic acid (crude product) as shown in a formula III; adding water, alcohol and other polar solvents into the 2-cyano-2-valproic acid crude product, pulping, carrying out gradient crystallization, filtering, and carrying out low-temperature vacuum drying to obtain 2-cyano-2-valproic acid monohydrate and 2-cyano-2-methylvalproic acid monohydrate; the 2-cyano-2-valproic acid monohydrate is subjected to high-temperature decarboxylation hydrolysis through sulfuric acid, and valproic acid is prepared; and carrying out high-temperature decarboxylation hydrolysis on the 2-cyano-2-methylpentanoic acid monohydrate by using sulfuric acid to obtain the essence 2-methylpentanoic acid.

This invention relates to the field of biomedical technology, specifically disclosing the application of betaine in the preparation of drugs for treating autism. Through experiments using a valproic acid-induced mouse model of autism spectrum disorder, this invention found that betaine can significantly improve social impairments and repetitive, stereotyped behaviors in the model mice, and exhibits stable and reproducible effects in both 1-month-old and 2-month-old male offspring. This invention reveals a novel use of betaine in treating core behavioral deficits in autism spectrum disorder (ASD), providing a new source of natural active ingredients for the preparation of drugs for treating autism.

The invention belongs to the technical field of medicine detection, and particularly relates to a high performance liquid chromatography detection method for dipropylmalonic acid and impurities thereof. The method comprises the following steps: preparing a to-be-detected sample into a test solution; the to-be-detected sample is dipropyl malonic acid prepared by adopting a diethyl malonate method and impurities of the dipropyl malonic acid; and detecting the test solution by adopting a high performance liquid chromatography method to obtain a detection result of dipropylmalonic acid and impurities thereof in the sample to be detected. According to the detection method provided by the invention, the detection of dipropylmalonic acid prepared by adopting a diethyl malonate method and impurities thereof is realized through high performance liquid chromatography (HPLC) for the first time, and the problems of quality control and process evaluation of the dipropylmalonic acid prepared by adopting the diethyl malonate method, which is an intermediate of a sodium valproate raw material medicine, are solved; therefore, detection and control of impurities (including 2-ethyl valeric acid) in the sodium valproate raw material medicine are realized.

The present technology generally relates to methods of treating social deficits with HDAC inhibitors. Select embodiments of the present technology include a method for treating organophosphate induced social deficits in a subject, comprising administering to a subject in need thereof a therapeutically effective amount of an HDAC inhibitor selected from the group consisting of valproic acid, butyric acid, BRD-6929, RGFP966, pharmaceutically acceptable salts thereof, and combinations thereof. The subject may have been diagnosed with a disease or disorder characterized by social deficits, such as autism spectrum disorder. The subject may be monitored for a change in the severity of social deficits.

The present invention relates to a combination of valproic acid (VPA) and S- adenosylmethionine (SAMe) for use in preventing congenital malformations in a fetus of a subject in need of VPA treatment and who is pregnant or intends to become pregnant, by administering the combination to the subject before or during the first trimester of pregnancy, wherein the SAMe and the VPA are at a ratio of about 1:10-1:50 w / w SAMe:VPA in the combination; and corresponding methods of treatment.

The present application relates to the technical field of pharmaceutical chemistry, and particularly relates to lithium valproate and crystal forms thereof, a preparation method therefor, a pharmaceutical composition thereof and the use thereof. The crystal forms of lithium valproate comprise crystal form I, crystal form II, crystal form III, crystal form IV, crystal form V, crystal form VI and crystal form VII.

The invention belongs to the technical field of biological medicine, and particularly relates to application of valproic acid in preparation of medicine for preventing and / or treating lung fibroblast and lung tissue senescence, the medicine induces the senescent lung fibroblast to excessively accumulate active oxygen in the cell, so that excessive autophagy of the cell is induced, senescent cell apoptosis is caused, and the effect of preventing and / or treating lung fibroblast and lung tissue senescence is achieved. And finally, the lung aging is relieved. The invention provides a new medicine source for preventing, intervening, delaying and researching aging of lung fibroblasts and lung tissues. The medicine for promoting apoptosis of aging cells in vitro or in the lung tissues, provided by the invention, is safe, relatively strong in pharmacological action, small in side effect and definite in curative effect.

A method for improving cognitive function of a subject which includes administering a composition containing dextromethorphan or valproic acid to the subject in need thereof. The composition containing the dextromethorphan is used for improving the sustained attention of the subject. The composition containing the valproic acid is used for improving the memory of the subject.

The application discloses a kind of HPLC-MSMS method for simultaneously determining valproic acid, olanzapine and its metabolites in plasma, which comprises the following steps: S1. pretreatment of plasma samples with acetonitrile protein precipitation method;S2. HPLC-MSMS method is used to detect plasma samples, and qualitative and / or quantitative analysis of valproic acid, olanzapine and its metabolites in plasma is carried out simultaneously;Wherein, Agilent Poroshell 120EC-C18 column is selected as the chromatographic column;Electrospray ion source is used, and the mobile phase is A phase: formic acid water, B phase: acetonitrile;By optimizing the conditions of liquid phase and mass spectrometry, valproic acid, olanzapine and its metabolites are simultaneously determined by one method.The method has been applied to detect plasma samples of olanzapine and valproic acid combination, and olanzapine alone, and the measured results all meet the linear range.

The invention belongs to the technical field of biological medicine and tumor immunotherapy, and discloses application of 3-oxo-valproic acid coenzyme A in preparation of a medicine for inhibiting lung adenocarcinoma. As a specific agonist of GIMAP1, the 3-oxo-valproic acid coenzyme A is used for activating the GIMAP1, enhancing inhibition of lung cancer cell progress and enhancing activation of a tumor immune microenvironment, so that the lung adenocarcinoma is inhibited, and the lung adenocarcinoma is inhibited. The invention has the following beneficial effects: 1, strong targeting property: 3-oxo-valproate coenzyme A is specifically combined with GIMAP1, so that a mediated immunomodulatory pathway is accurately activated, and wide influence on normal cells is avoided; 2, immune microenvironment remodeling: the anti-tumor immune cell infiltration is remarkably improved, the lung adenocarcinoma immunosuppression microenvironment is reversed, and the immunotherapy sensitivity is improved; 3, tumor progression is inhibited, lung cancer cell proliferation is effectively inhibited, and the tumor invasion ability is reduced; 4, the source is natural: as an intestinal microbial metabolite derivative, the safety is high, and the side effect is lower than that of a chemically synthesized medicine.

This invention belongs to the field of medicinal chemistry and discloses a compound and its use. The compound, represented by Formula I, or its stereoisomers, provided herein can effectively alleviate behavioral disturbances exhibited in a rat model of autism induced by valproic acid, providing a potential candidate for the development of novel autism treatments.

The present invention relates to valproic acid for use in treating and / or preventing pulmonary arterial hypertension (PAH), wherein the treatment and / or prevention comprises administering to a subject a total daily dose of from about 200 mg to about 600 mg of valproic acid or a pharmaceutically acceptable salt thereof.

The invention discloses application of valproic acid in preparation of a medicine for resisting jewfish iridovirus. 24 mM of VPA is non-toxic to LJFin, and the effective use concentration of VPA for inhibiting SPIV infection in in-vitro cells is 3-24 mM. Through three administration modes of pretreatment, co-treatment and post-treatment, the VPA has the effects of preventing and treating SPIV infection. The VPA plays a role in resisting SPIV infection mainly by inhibiting entry and release of viruses, and has no obvious influence on adsorption of the viruses. In addition, after being fed as a feed additive, the feed additive does not affect ingestion and fish body health, and shows a good ability of enhancing the SPIV resistance of jewfish. According to the present invention, the death rate caused by SPIV infection is reduced by adding 0.25% and 0.5% of the VPA to the feed, the relative protection rates on SPIV are 21.1% and 31.6%, the virus replication in the tissue can be inhibited, and the virus-induced fish target tissue structure damage can be reduced; as an antiviral drug, VPA has a certain application value in prevention and control of jewfish iridovirus diseases.

The present disclosure relates to a combination of valproic acid or a pharmaceutically acceptable salt thereof, a β-lactam compound or a pharmaceutically acceptable salt thereof, and probenecid or a pharmaceutically acceptable salt thereof. The present disclosure also relates to methods of treating or preventing disease using this combination.

This application relates to the field of analytical detection technology, specifically to sample pretreatment methods, kits, and detection methods for the detection of antiepileptic drugs. The sample pretreatment method for the detection of antiepileptic drugs in this application includes one or more of the following antiepileptic drugs: valproic acid, carbamazepine, phenytoin, levetiracetam, lamotrigine, and phenobarbital. The sample pretreatment method includes the following steps: mixing magnetic beads with an activation solution to prepare a magnetic bead suspension; mixing the sample to be tested, the magnetic bead suspension, and an internal standard solution, and separating the supernatant and the magnetic bead complex after magnetic adsorption treatment; adding an eluent to the magnetic bead complex, and collecting the magnetic bead-target complex after elution treatment; adding an elution buffer to the magnetic bead-target complex, and collecting the supernatant after elution treatment for detection. The above sample pretreatment method is simple to operate, time-saving, and low-cost, providing key technical support for the efficient quantitative detection of antiepileptic drugs.

The present application relates to a method for detecting impurities in valproic acid or sodium valproate prepared by methyl cyanoacetate method by gas chromatography, characterized in that the impurities in valproic acid or sodium valproate prepared by methyl cyanoacetate method are detected by gas chromatography; the impurities are selected from valeric acid (A), 2-methyl valeric acid (L), 2-isopropyl valeric acid (C), valproic amide (F) or 2-propyl hexanoic acid (X):

The invention relates to the field of biological medicine, in particular to a three-component platinum (IV) complex containing captopril (CTP) and valproic acid (VPA), a preparation method of the three-component platinum (IV) complex and application of the three-component platinum (IV) complex in preparation of anti-tumor proliferation and anti-metastasis drugs. The anti-tumor proliferation and anti-metastasis effects of the target compound are tested through in-vivo and in-vitro testing means, and the anti-tumor mechanism of the medicine is researched. Results prove that the compound has a remarkable anti-tumor capability, particularly has an excellent treatment effect on metastatic malignant tumors, is expected to provide a new candidate drug for clinical treatment of tumors, and provides a new direction for research and development of novel platinum drugs and anti-tumor metastasis drugs.

Disclosed herein are improved methods of producing recombinant adeno-associated viruses (rAAVs) for gene therapy. The improved method comprises adding low doses of DMSO and valproic acid to a cell transfected with a plasmid encoding the rAAV and a plasmid containing a cofactor for expressing and / or assembling the rAAV capsid.

The invention relates to a pharmaceutical composition for oral administration. The pharmaceutical composition comprises: a) immediate release particles comprising i. An active ingredient selected from the group consisting of valproic acid, semi-sodium valproate, sodium valproate and magnesium valproate, and ii. A filler, b) sustained release pellets comprising: i. A pellet core comprising (1) an active ingredient selected from the group consisting of valproic acid, semi-sodium valproate, sodium valproate and magnesium valproate, and (2) a filler, ii. A sub-coating disposed on the pellet core, the content of the sub-coating layer is 10-20 wt% based on the weight of the pellet core and the sub-coating layer comprises a film-forming agent, and iii. A slow-release coating layer disposed on the sub-coating layer, the content of the slow-release coating layer is 25-100 wt% based on the weight of the pellet core coated with the sub-coating layer and the slow-release coating layer comprises a film-forming agent, and the content of the slow-release coating layer is 25-100 wt% based on the weight of the pellet core coated with the sub-coating layer. Wherein the amount of the active ingredients in the quick-release particles accounts for 70-80 wt% of the total weight of the active ingredients in the pharmaceutical composition, and the amount of the active ingredients in the slow-release pellets accounts for 20-30 wt% of the total weight of the active ingredients in the pharmaceutical composition. In further aspects, the present invention relates to methods of preparing pharmaceutical compositions and pharmaceutical compositions for use in methods of pre-treating cancer.

The application discloses a valproic acid detection kit. Specifically, the application relates to a valproic acid derivative and a preparation method thereof, and a kit containing the valproic acid derivative and a preparation method thereof. The technical scheme of the application uses a novel valproic acid derivative and a coupling method of maleimide-sulfhydryl with high selectivity, so that the derivative and an enzyme are coupled in a 1:1 mode, and batch difference formed in a conventional coupling process is greatly reduced. The valproic acid detection kit is simple, fast and low in cost, and can be automatically detected on various mainstream machines.

The invention provides a composition for reversing organ fibrosis and application of the composition, and belongs to the technical field of biological medicines.The cocktail composition is prepared from valproic acid, CHIR99021, Repsox, trans-benzene ring propylamine and forskolin. The HAT inhibition composition is prepared from A485 and WM-8014; the cocktail composition and the HAT inhibition composition are used independently or jointly, and hepatic fibrosis or pulmonary fibrosis can be reversed; when the composition is used in combination, a synergistic enhancement effect is shown in pulmonary fibrosis and hepatic fibrosis models, and the effects of improving fibrosis indexes and reversing epigenetic age are more remarkable; according to the composition provided by the invention, the epigenetic procedure of cells is accurately controlled, so that the cells are safely reversed from a pathological state to a healthy or resting state, the pathological phenotype of fibrosis is improved, the biological age of the cells is fundamentally reversed, and a major breakthrough in the field of fibrosis treatment is represented.

A method of intranasal drug delivery including administering a multi-compartment nanoemulsion to a nasal cavity of a subject in need thereof, where the multi-compartment nanoemulsion includes a water-in-oil core emulsion having an oil phase encompassing a first aqueous phase, the oil phase comprising a first surfactant and a fatty acid and the first aqueous phase comprising levetiracetam and valproic acid dissolved therein. The multi-compartment nanoemulsion further includes a second aqueous phase encompassing the water-in-oil core emulsion, the second aqueous phase comprising a second surfactant and a co-surfactant in a ratio of the second surfactant to the co-surfactant of 1:4 to 4:1. The multi-compartment nanoemulsion has an average droplet size of less than 100 nm and a polydispersity index (PDI) of 0.1 to 0.2.

The invention relates to the technical field of analysis and detection, in particular to a sample pretreatment method for anti-epileptic drug detection, a kit and a detection method. According to the sample pretreatment method for anti-epileptic drug detection, an anti-epileptic drug comprises one or more of valproic acid, carbamazepine, phenytoin, levetiracetam, lamotrigine and phenobarbital; the sample pretreatment method comprises the following steps: mixing magnetic beads with an activating solution to prepare a magnetic bead suspension; mixing a to-be-detected sample, the magnetic bead suspension and the internal standard solution, performing magnetic attraction treatment, and separating supernate and a magnetic bead compound; leacheate is added into the magnetic bead compound, and after leaching treatment, a magnetic bead-target compound is collected; and adding an eluent into the magnetic bead-target compound, carrying out elution treatment, and collecting a supernatant for detection. The sample pretreatment method is simple to operate, short in time consumption and low in cost, and can provide key technical support for efficient quantitative detection of the anti-epileptic drugs.

A stable pharmaceutical composition in the form of orally administrable prolonged release tablet comprising sodium valproate and valprioic acid with no granulating solvent is disclosed, further comprising low viscosity polymer, high viscosity polymer, binder, adsorbent and glidant. A process for the preparation of said orally administrable prolonged release tablet is also disclosed.